Opioid receptors as a drug target for stopping obesity

ScienceDaily (July 31, 2012) — New research demonstrates that blocking the delta opioid receptor in mice created resistance to weight gain and stimulated gene expression promoting non-shivering thermogenesis.

See Also:Health & MedicineDiet and Weight LossObesityFitnessMind & BrainDieting and Weight ControlOpiumNutrition ResearchLiving WellReferenceDetox dietSouth Beach dietCalorie restricted dietAdipose tissue

Imagine eating all of the sugar and fat that you want without gaining a pound. Thanks to new research published in The FASEB Journal, the day may come when this is not too far from reality. That's because researchers from the United States and Europe have found that blocking one of three opioid receptors in your body could turn your penchant for sweets and fried treats into a weight loss strategy that actually works. By blocking the delta opioid receptor, or DOR, mice reduced their body weight despite being fed a diet high in fat and sugar. The scientists believe that the deletion of the DOR gene in mice stimulated the expression of other genes in brown adipose tissue that promoted thermogenesis.

"Our study provided further evidence that opioid receptors can control the metabolic response to diets high in fat and sugar, and raise the possibility that these gene products (or their respective pathways) can be targeted specifically to treat excess weight and obesity," said Traci A. Czyzyk, Ph.D., a researcher involved in the work from the Department of Physiology at the Mayo Clinic in Scottsdale, Arizona.

Scientists studied mice lacking the delta opioid receptor (DOR KO) and wild type (WT) control mice who were fed an energy dense diet (HED), high in fat and sugar, for three months. They found that DOR KO mice had a lean phenotype specifically when they were fed the HED. While WT mice gained significant weight and fat mass on this diet, DOR KO mice remained lean even though they consumed more food. Researchers then sought to determine how DOR might regulate energy balance and found that DOR KO mice were able to maintain their energy expenditure levels, in part, due to an increase in non-shivering thermogenesis. This was evidenced by an increase in thermogenesis-promoting genes in brown adipose tissue, an increase in body surface temperature near major brown adipose tissue depots, and the ability of DOR KO mice to maintain higher core body temperatures in response to being in a cold environment.

"Don't reach for the ice cream and doughnuts just yet," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "We don't know how all this works in humans, and of course, a diet of junk food causes other health problems. This exciting research identifies genes that activate brown adipose tissue to increase our burning of calories from any source. It may lead to a safe diet pill in the future."

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Developing world has less than 5% chance of meeting UN child hunger target, study estimates

ScienceDaily (July 5, 2012) — Insufficient progress has been made in most developing countries to meet the United Nations' target of halving the proportion of children who suffer from hunger by 2015 compared with 1990 levels, according to a systematic analysis of data on children's height and weight, published July 5 in the Lancet. Although the nutritional status of children under five has improved overall since 1985, one in five infants and children in developing countries is still moderately or severely underweight, amounting to an estimated 110 million children worldwide. Another 148 million are mildly underweight.

See Also:Health & MedicineChildren's HealthDiet and Weight LossInfant's HealthScience & SocietyPublic HealthWorld DevelopmentEducational PolicyReferenceBody mass indexMicronutrientMalnutritionOverweight

The UN set the target as part of its Millennium Development Goals. This new analysis, led by Professor Majid Ezzati from the School of Public Health at Imperial College London, estimates that while 61 out of the 141 developing countries studied are likely to meet this target, the developing world as a whole has less than a 5% chance of succeeding. Progress has been uneven between regions, with Asia and Latin America making the strongest improvements and sub-Saharan Africa falling behind.

Because nutrition has a strong effect on children's growth, nutritional status in children can be assessed using scores based on their height and weight relative to their age, called height-for-age and weight-for-age Z scores (HAZ and WAZ).

Researchers from Imperial College London, the World Health Organisation and universities in the US compiled HAZ and WAZ data from national surveys and other sources, and used statistical methods to estimate average Z scores and the prevalence of undernutrition (defined as insufficient food intake and absorption) for entire countries.

The results show that:

• The proportion of children classed as moderately to severely underweight fell from 30.1% to 19.4% between 1985 and 2011 in the countries studied. The prevalence of moderate to severe stunting (insufficient growth in height for their age) declined from 47.2% to 29.9%.

• South Asia, the region with the worst nutritional status in 1985, has improved considerably, but undernutrition is still a major issue. About one half of the world's underweight children live in South Asia, mostly in India.

• Undernutrition worsened in sub-Saharan Africa from 1985 until the late 1990s, when height and weight scores began to improve. The deterioration may have been due to economic shocks, structural adjustment, and trade policy reforms in the region in the 1980s and 1990s.

• In Ivory Coast and Niger, nutritional status was measurably worse in 2011 than it had been in 1985.

• Height and weight scores improved in all other regions, with the largest improvements in South Asia, East and Southeast Asia, and Southern and Tropical Latin America. The biggest improvement in children's height occurred in China and Vietnam.

• Some countries in Latin America, such as Chile, now have almost no undernutrition. The proportion of underweight children almost halved per decade in Brazil.

• As of 2011, about half of children in Burundi, Yemen, Timor-Leste, Niger and Afghanistan are moderately or severely stunted. More than one third of children in Timor-Leste, Bangladesh, Niger, India and Nepal are moderately or severely underweight.

This new study includes estimates of all levels of malnutrition, unlike previous analyses, which excluded children who were mildly malnourished. The statistics suggest that in most countries, the improvements are due to population-wide improvements in nutrition, rather than interventions targeting high-risk children.

Professor Majid Ezzati said: "Our analysis shows that the developing world as a whole has made considerable progress towards reducing child malnutrition, but there are still far too many children who don't receive sufficient nutritious foods or who lose nutrients due to repeated sickness. Severe challenges lie ahead.

"There is evidence that child nutrition is best improved through equitable economic growth, investment in policies that help smallholder farmers and increase agricultural productivity, and primary care and food programmes targeted at the poor. We mustn't allow the global economic crisis and rising food prices to cause inequalities to increase, or cut back on investments in nutrition and healthcare."

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Chronic diseases are health ministers' target -WHO

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WHO target to cut early chronic illness deaths

"An Indian nurse collects a blood sample from a patient using a glucometer at a diabetic health check up centre in Hyderabad. The World Health Organization has announced it is set to approve a new target to reduce premature deaths from chronic illnesses such as heart disease by a quarter by 2025. (AFP Photo/Noah Seelam)" title

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Diabetes drug target identified

ScienceDaily (May 21, 2012) — New research from the University of Cincinnati (UC) points to the naturally produced protein apolipoprotein A-IV (apoA-IV) as a potential target for a new diabetes therapeutic.

See Also:Health & MedicineDiabetesDiet and Weight LossObesityHormone DisordersGastrointestinal ProblemsEpilepsy ResearchReferenceBlood sugarDiabetic dietHyperglycemiaDiabetes mellitus type 2

Patrick Tso, PhD, professor in the UC Department of Pathology and Laboratory Medicine, has published research on the ability of apoA-IV to reduce blood sugar levels and enhance insulin secretion.

The results appear the week of May 21, 2012, in the online early edition of Proceedings of the National Academy of Sciences.

ApoA-IV is secreted by the small intestine in response to fat absorption. Previous studies have shown apoA-IV to be elevated in humans following gastric bypass -- coinciding with improvement in symptoms for diabetes.

The Tso team found that mice deficient in apoA-IV had impaired glucose tolerance (insulin was not secreted to move glucose from the blood stream). These mice also developed diabetes when continuously fed a high-fat diet. When injected with apoA-IV, these same mice showed improved insulin response to glucose, despite a diet high in fat.

Tso's team also tested the response to injected apoA-IV in diabetic mice and found it reduced glucose levels among that group as well.

Tso says their research shows apoA-IV to behave similar to an incretin -- a gastrointestinal hormone causing an increased release of insulin after eating to combat the onset of elevated blood glucose. Two well-known incretins that have been used in the development of existing diabetes medications include gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1).

"The problem with both of these incretins is that they are short-lived -- lasting only for minutes -- and are quickly inactivated by an enzyme," says Tso. "They have also been linked to hypoglycemia, or low blood sugar, when administered when the body has a low glucose concentration. The challenge is to find something safer with a longer half-life."

Tso says apoA-IV has a long half-life (between seven and eight hours) and that tests in his lab showed it to have no effect on glucose levels when administered at low glucose concentrations. Instead, he says, it seems to function to normalize glucose.

The University of Cincinnati has licensed this research finding to a startup biotech company, Apofore Corporation, formed by HealthCare Ventures of Cambridge, Mass. Apofore will further study apoA-IV in humans in an effort to develop a novel diabetes therapeutic.

Tso's research was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

Co-authors include Sean Davidson, PhD, Tammy Kindel, Alison Kohan, Silvana Obici, PhD, Fei Wang and Stephen Woods, PhD, all from the University of Cincinnati; and Kathryn Corbin and Craig Nunemaker of the University of Virginia, Charlottesville.

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French medical orders target diet guru Pierre Dukan

"Doctor Pierre Dukan is pictured in 2011. French medical orders have filed complaints against the celebrity diet guru whose diet was reportedly used by the Middleton family ahead of Kate's wedding to Britain's Prince William. (AFP Photo/Loic Venance)" title

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